Specific recognition of two MAX effectors by integrated HMA domains in plant immune receptors involves distinct binding surfaces

Abstract

SignificanceIn this study, we provide insight into the mechanism of effector recognition by plant nucleotide-binding domain and leucine-rich repeat proteins (NLRs), a ubiquitous class of immune receptors that plays a central role in crop protection. By structural and functional analysis of a complex between a fungal effector and an integrated decoy domain (ID) from a rice NLR, we demonstrate the importance of IDs in effector recognition and generate crucial knowledge for future engineering of NLRs to expand their recognition specificities. In addition, we propose, as a hypothesis regarding the diversity of fungal effectors, that in structurally conserved effector families, the molecular mechanisms of host target protein-binding are conserved but not the host target proteins themselves.

Cross-reactivity of a rice NLR immune receptor to distinct effectors from the blast pathogen leads to partial disease resistance

“…The discovery that rice blast pathogen effectors with a common structural fold can be recognised by the same type of integrated domain in rice NLRs raises questions about specificity, and possible plasticity of recognition. M. oryzae MAX effectors AVR-PikD and AVR1-CO39 are bound at different interfaces by their respective NLR-encoded HMA domains (11,12,29). Here, we investigated the interaction of a "mis-matched" NLR integrated domain (Pikp-HMA) and pathogen effector (AVR-Pia), to better understand how protein interfaces contribute to signalling.…”

“…The cross-reactivity of Pikp for the "mis-matched" AVR-Pia effector raises exciting possibilities around engineering Pikp to respond more robustly to this effector, whilst maintaining AVR-PikD interactions. As noted by Guo et al, the use of different interfaces for the effectors may allow engineering of one surface without significantly disrupting the binding at the other (29). Such detailed structural knowledge paves the way towards future NLR engineering for improved disease resistance that may be applicable to other NLR/effector pairs.…”

“…Intriguingly, while Pikp-HMA binds AVR-Pia at a different interface to AVR-PikD, it uses the same interface that RGA5-HMA uses to bind AVR1-CO39 (29). Therefore, a single integrated domain in a plant NLR can interact with divergent effectors via different surfaces.…”

“…S4). Like Pikp-HMA, RGA5-HMA forms a dimer in solution, and binding to the effector competes with this, such that only an HMA monomer is present in each complex (29). Globally, the complexes are very similar, and both rely heavily on peptide backbone interactions for maintaining an interaction between the HMA and effector.…”

“…The interface between AVR-Pik effectors and the HMA domain of both Pikp and Pikm has been extensively studied and structurally characterised (11,12). Recently, the structure of AVR1-CO39 in complex with the HMA domain of RGA5 was also elucidated (29), and revealed that the HMA/effector interface was substantially different compared to the Pik NLR pairs. This has raised intriguing questions concerning how structurally similar but sequence divergent HMA domains distinguish between structurally similar but sequence divergent pathogen effectors.…”